Combination of ET with inhibitors for cyclin dependent kinase 4/6 (CDK4/6), mammalian target of rapamycin (mTOR), or phosphatidylinositol-4,5- biphosphate 3-kinase catalytic subunit alpha (PIK3CA) is integral part of the treatment in metastatic ER+ breast cancer and represent major improvements in progression free survival (28). This evidence concerns the gene CDK4 and breast carcinoma.